The human DNA sequence homologous to v-mos, the transforming gene of Moloney murine sarcoma virus (MoMSV), contains a polypeptide coding sequence that is 75% homologous to the mouse cellular mos (c-mosmu). Neither the mouse nor human (c-moshu) sequence are capable of transforming NIH 3T3 cells. However, c-mosmu can be activated to transform mouse cells when linked to the long terminal repeat sequence (LTR) of MoMSV. Similar LTR-c-moshu recombinants are inactive in this assay. To locate the specific regions of the c-moshu coding region responsible for inactivity a series of mos gene hybrids were generated in E. coli. between c-moshu and v-mos. Analysis of v-mos/c-moshu hybrid recombinants have revealed that specific regions of the c-moshu locus, which when subsituted with v-mos specific sequences a novel way can actively function as a transforming gene. These analyses have provided for identifying domains in mos required for transforming activity. For example, we have identified a maximum of five amino acid differences between v-mos and c-moshu that could prevent the latter from being biologically active. These results demonstrate that the c-moshu oncogene requires both qualitative and quantitative changes in order to be activated as a transforming gene. A dominant transforming gene has been identified from the human pancreatic cell line PANC-1. Better than 70% of this gene has been cloned in prokaryotic vectors. It appears to be a member of a family of human sequences related to the Kirsten ras oncogene.